A variety of flavorants have been developed and proposed for incorporation into tobacco products. Illustrative of such tobacco flavorants are those described in U.S. Pat. Nos. 3,580,259; 3,625,224; 3,722,516; 3,750,674; 3,879,425; 3,881,025; 3,884,247; 3,890,981; 3,903,900; 3,914,451; 3,915,175, 3,920,027; 3,924,644; 3,937,228; 3,943,943; 3,586,387; and the like. The tobacco flavorants include compounds such as succinic anhydride; dihydroxyacetone; substituted pyridines; cinnamic derivatives; isovaleric acid; 6-methylhepta-3,5-dien-2-one; 2-butyl-2-butenal; 1,3-cyclohexadiene; alpha-pyrones; substituted butyrolactones; pyrazines and thiazolidines; and the like.
Cooling compounds, particularly methanol, have been used extensively in tobacco products. Unfortunately methanol has a high degree of volatility and also suffers from the disadvantage that it exhibits a relatively strong minty odor. Nevertheless, in spite of its disadvantages methanol is still extensively employed as a tobacco flavorant for the reason it has a physiological cooling effect on the mucous membranes of the mouth. Methanol flavorant in cigarette tobacco produces a cool sensation in the mouth during the smoking of a cigarette.
Other organic compounds are known which exhibit to some degree the properties of a physiological coolant. For example, N,N-dimethyl-2-ethylbutanamide is reported in French Pat. No. 1,572,332 as having a minty odor and a refreshing effect on mucous membranes. Other compounds of similar interest are 2,4,6-trimethylheptan-4-ol and 2,4,6-trimethylhept-2-en-4-ol as reported in Parfums-Cosmetiques-Savons, pages 17-20, May 1956.
More recently another group of organic compounds have been developed which are odorless and non-volatile, and which can function as physiologically active coolants. These compounds are the subject matter of the U.S. Pat. Nos. 4,178,459 and 4,193,936, and are generically classified as N-substituted para-methane carboxamides. Illustrative of a particularly interesting species as a prospective smoking tobacco flavorant is N-t-butyl-p-menthane-3-carboxamide: ##STR1##
The said patents describe a sequence of conventional reactions for producing the N-substituted para-menthane carboxamides. Thus, N-t-butyl-p-menthane-3-carboxamide is produced by the following sequence of reactions: ##STR2##
The reaction sequence is long and tedious, and the overall conversion from 3-p-methyl halide to N-t-butyl-p-menthane-3-carboxamide is inefficient.
In copending patent application Ser. No. 258,207, filed Apr. 27, 1981, there is described a novel process for producing N-(hydrocarbyl)substituted-p-menthane-3-carboxamide compounds in general, and N-t-butyl-p-menthane-3-carboxamide in particular. The said novel process in a preferred embodiment comprises (1) reacting 3-p-methyl halide with magnesium in an anhydrous solvent medium to form 3-p-methylmagnesium halide; and (2) reacting the 3-p-methylmagnesium halide with t-butyl isocyanate to form N-t-butyl-p-menthane-3-carboxamide product.
A noteworthy aspect of the said novel process is that the N-t-butyl-p-menthane-3-carboxamide product is a mixture of 3-p-menthyl and 3-p-neomenthyl geometric isomers. When step (2) of the process is conducted at a temperature between about 0.degree.-30.degree. C., the quantity of the 3-p-menthyl isomer present in the isomer product mixture varies in the range between about 57-80 weight percent, based on the combined weight of the 3-p-menthyl and 3-p-neomenthyl isomers.
The relative ratio of 3-p-menthyl to 3-p-neomenthyl isomers in the final product is generally felt to be a significant factor when the physiological coolant properties of the said isomeric mixture is of primary importance.
It is well known that the p-menthane structure can exist in cis and trans forms. Substitution of a group (e.g., carboxamide) into the 3-position gives rise to four geometric isomers, depending upon whether the substituted group in the 3-position is an axial or equatorial configuration in each of the cis or trans isomers. The four geometric isomers are related as menthol is to neomenthol, isomenthol and neoisomenthol.
In general, it is found that among p-menthane-3-carboxamide compounds the equatorial 3-carboxamide derivatives (i.e., a 3-p-menthyl configuration) have a greater physiological coolant effect than do the axial 3-carboxamide derivatives (i.e., a 3-p-neomethyl configuration). Since they have superior physiological coolant properties, p-menthane-3-carboxamide isomers are much preferred over p-neomenthane-3-carboxamide isomers for applications such as tobacco flavorants.
Accordingly, it is a main object of this invention to provide an improved process for producing N-(hydrocarbyl)substituted-p-methane-3-carboxamide compounds.
It is a further object of this invention to provide an improved process for converting 3-p-menthyl halide to N-(hydrocarbyl)substituted-p-menthane-3-carboxamide, wherein the 3-carboxamide product comprises a mixture of 3-p-menthyl and 3-p-neomenthyl isomers in which the content of 3-p-menthyl isomer is at least about 90 weight percent, and the content of 3-p-neomenthyl isomer is less than about 10 weight percent.
Other objects and advantages of the present invention will become apparent from the accompanying description and examples.